基于Keap1/Nrf2与TLR4/NF-κB信号通路研究啶虫脒暴露对斑马鱼的免疫毒性及机制
Exploring the Immunotoxicity and Mechanisms of Acetamiprid Exposure in Zebrafish Based on the Keap1/Nrf2 and TLR4/NF-κB Signaling Pathways
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摘要: 为探究环境浓度啶虫脒(ACE)暴露对斑马鱼仔鱼的免疫毒性及作用机制，将5 dpf的斑马鱼仔鱼暴露在不同浓度的ACE溶液中，于10 dpf分析ACE暴露对斑马鱼仔鱼氧化应激水平、先天和适应免疫细胞、免疫相关参数及基因转录水平的影响。结果表明，ACE暴露导致仔鱼体内活性氧(ROS)的蓄积和抗氧化酶(包括超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶)活性的抑制；先天免疫细胞(巨噬细胞和中性粒细胞)数量和胸腺T细胞的面积显著减少；免疫相关参数中溶菌酶(LYS)的含量降低，一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)和免疫球蛋白M (IgM)的分泌量则显著升高。机制研究发现，ACE暴露可通过抑制Nrf2-Keap1通路，导致ROS的累积，从而引起机体氧化应激；可通过激活TLR4/NF-κB通路，诱导TNF-α、IL-6和IL-1β分泌，从而引起炎症反应。综上所述，环境浓度啶虫脒暴露对斑马鱼仔鱼的抗氧化防御系统和免疫系统造成了显著损害，这一过程可能与TLR4/NF-κB和Nrf2-Keap1信号通路相关。Abstract: This study aims to investigate the immunotoxicity and underlying mechanisms of environmental concentrations of acetamiprid (ACE) on zebrafish larvae. Zebrafish larvae were exposed to varying concentrations of ACE solution for 5 days post-fertilization (5dpf), and the effect of ACE on oxidative stress levels, innate and adaptive immune cells, immune related parameters, and gene transcription levels of zebrafish larvae were analyzed at 10 dpf. The results indicated that ACE exposure led to the accumulation of reactive oxygen species (ROS) and inhibition of antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase in juvenile fish. Additionally, there was a significant decrease in the number of innate immune cells (macrophages and neutrophils) and T cells. Moreover, the content of lysozyme (LYS) in immune-related parameters decreased, while the secretion of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and immunoglobulin M (IgM) significantly increased. Mechanism studies revealed that ACE exposure can (1) lead to the accumulation of ROS by inhibiting the Nrf2-Keap1 pathway, resulting in oxidative stress in the body; (2) induce the secretion of TNF-α, IL-6, and IL-1β by activating the TLR4/NF-κB pathway, thereby triggering an inflammatory response. In summary, exposure to environmental concentration, acetamiprid caused significant damage to the antioxidant defense system and immune system of zebrafish larvae, which may be related to TLR4/NF-κB and Nrf2-Keap1 signaling pathways.
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Key words:
- pesticide /
- acetamiprid /
- zebrafish /
- immunotoxicity /
- molecular mechanisms
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